Two interesting cases:  Glucagonoma Syndrome and Glucagonoma in MEN1 syndrome


Y Khalid, G Bano, St George’s Hospital.


Glucagonoma syndrome is extremely rare with an estimated prevalence of 1 in 20 million.  Necrolytic migratory erythema is the presenting manifestation in most cases. Glucagonomas may occur in Multiple Endocrine Neoplasia syndrome 1 (MEN 1), although this association is rare. We present cases, the first with glucagonoma syndrome and the second as a part of MEN1 syndrome.


Case 1. 64 year old gentleman presented with a maculo-papular rash on his left leg that settled with a topical cream but re-appeared after a year on his legs, arm, chest and back. Histology showed necrolytic migratory erythema rash. His glucagon level was elevated at 348 pmol/l (normal range 0-50) with high chromogranin A and B at 74 pmol/l (normal range <60 pmol/l)) and 257 pmol/l (normal range <150) respectively. IGF1, prolactin, TSH, FT4, LH, FSH, testosterone, PTH, adjusted calcium, LFTs, somatostatin, gastrin, VIP, pancreatic polypeptide were all in normal range. Oral glucose tolerance test confirmed diabetes mellitus. Genetic testing for MEN1 gene mutation was negative. CT pancreas showed a large heterogeneous mass in the tail of the pancreas with at least two large peri-pancreatic nodes. The elongated abnormality was approximately 10 cm long. The head and neck of the pancreas were normal.  The appearances in the tail were consistent with glucagonoma. Octreotide scan with SPECT showed low grade uptake within the body of the pancreas with a more focal and intense uptake in the discrete masses within the tail of the pancreas as well as adjacent lymph nodes. He underwent subtotal distal pancreatectomy and splenectomy. Histology showed well differentiated grade 2 neuroendocrine tumour of pancreas measuring 7.1 cm in diameter, with vascular invasion and positive lymph nodes. He is now on monthly Octreotide injections, his skin rash improved, his diabetes medications were stopped.


Case 2. 35 year old gentleman presented with primary hyperparathyroidism and renal calculi in 2008. He underwent total parathyroidectomy and partial thyroidectomy in 2008 followed by medial sternal parathyroid removal in 2010 when he became hypercalcaemic again. He remained normocalcaemic afterwards.  Genetic test for MEN1 mutation gene were positive. 4 years later on surveillance screening his glucagon and chromogranin A levels were elevated.  CT and MRI scan showed 2 cystic lesions in the pancreas and a 4.0 x 1.8 cm abnormality arising from the posterior aspect of the tail of pancreas which was octreotide avid. EUS showed hypertensive lesions in the tail of the pancreas, FNA was inadequate. He had distal pancreatectomy and splenectomy in 2012, histology showed six well differentiated neuroendocrine tumours; all were grade 1 with R1 resections. Post-operative imaging showed a small volume mass lesion in the head of pancreas and at the resection margin of the pancreas that has not increased in size since 2012. The lesions were octreotide negative. His glucagon levels started to increase gradually.  His VIP, pancreatic polypeptide, gastrin, somatostatin, chromogranin A, adjusted calcium and pituitary function tests have been normal. In 2014 glucagon level rose to 122. He underwent repeat surgery in May 2015 on a 7mm arterial enhancing nodule. Histology was in keeping with a hemangioma. Post operatively glucagon levels have dropped. He will be considered for octreotide treatment.